Mycotoxin
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A mycotoxin (from the Greek μύκης mykes, "fungus" and τοξίνη toxini, "toxin")[1][2] is a toxic secondary metabolite produced by organisms of kingdom Fungi[3][4] and is capable of causing disease and death in both humans and other animals.[5] The term 'mycotoxin' is usually reserved for the toxic chemical products produced by fungi that readily colonize crops.[6]
Most fungi are aerobic (use oxygen) and are found almost everywhere in extremely small quantities due to the diminute size of their spores. They consume organic matter wherever humidity and temperature are sufficient. Where conditions are right, fungi proliferate into colonies and mycotoxin levels become high. The reason for the production of mycotoxins is not yet known; they are not necessary for the growth or the development of the fungi.[8] Because mycotoxins weaken the receiving host, they may improve the environment for further fungal proliferation. The production of toxins depends on the surrounding intrinsic and extrinsic environments and these substances vary greatly in their toxicity, depending on the organism infected and its susceptibility, metabolism, and defense mechanisms.[9]
Aflatoxins are a type of mycotoxin produced by Aspergillus species of fungi, such as A. flavus and A. parasiticus.[10] The umbrella term aflatoxin refers to four different types of mycotoxins produced, which are B1, B2, G1, and G2.[11] Aflatoxin B1, the most toxic, is a potent carcinogen and has been directly correlated to adverse health effects, such as liver cancer, in many animal species.[10] Aflatoxins are largely associated with commodities produced in the tropics and subtropics, such as cotton, peanuts, spices, pistachios, and maize.[10][11]
Ochratoxin is a mycotoxin that comes in three secondary metabolite forms, A, B, and C. All are produced by Penicillium and Aspergillus species. The three forms differ in that Ochratoxin B (OTB) is a nonchlorinated form of Ochratoxin A (OTA) and that Ochratoxin C (OTC) is an ethyl ester form Ochratoxin A.[12] Aspergillus ochraceus is found as a contaminant of a wide range of commodities including beverages such as beer and wine. Aspergillus carbonarius is the main species found on vine fruit, which releases its toxin during the juice making process.[13] OTA has been labeled as a carcinogen and a nephrotoxin, and has been linked to tumors in the human urinary tract, although research in humans is limited by confounding factors.[12][13]
Fusarium toxins are produced by over 50 species of Fusarium and have a history of infecting the grain of developing cereals such as wheat and maize.[18][19] They include a range of mycotoxins, such as: the fumonisins, which affect the nervous systems of horses and may cause cancer in rodents; the trichothecenes, which are most strongly associated with chronic and fatal toxic effects in animals and humans; and zearalenone, which is not correlated to any fatal toxic effects in animals or humans. Some of the other major types of Fusarium toxins include: enniatins such as beauvericin), butenolide, equisetin, and fusarins.[20]
Although various wild mushrooms contain an assortment of poisons that are definitely fungal metabolites causing noteworthy health problems for humans, they are rather arbitrarily excluded from discussions of mycotoxicology. In such cases the distinction is based on the size of the producing fungus and human intention.[15] Mycotoxin exposure is almost always accidental whereas with mushrooms improper identification and ingestion causing mushroom poisoning is commonly the case. Ingestion of misidentified mushrooms containing mycotoxins may result in hallucinations. The cyclopeptide-producing Amanita phalloides is well known for its toxic potential and is responsible for approximately 90% of all mushroom fatalities.[21] The other primary mycotoxin groups found in mushrooms include: orellanine, monomethylhydrazine, disulfiram-like, hallucinogenic indoles, muscarinic, isoxazole, and gastrointestinal (GI)-specific irritants.[22] The bulk of this article is about mycotoxins that are found in microfungi other than poisons from mushrooms or macroscopic fungi.[15]
In the 1990s, public concern over mycotoxins increased following multimillion-dollar toxic mold settlements. The lawsuits took place after a study by the Center for Disease Control (CDC) in Cleveland, Ohio, reported an association between mycotoxins from Stachybotrys spores and pulmonary hemorrhage in infants. However, in 2000, based on internal and external reviews of their data, the CDC concluded that because of flaws in their methods, the association was not proven. Stachybotrys spores in animal studies have been shown to cause lung hemorrhaging, but only at very high concentrations.[26]
Mycotoxins in animal fodder, particularly silage, can decrease the performance of farm animals and potentially kill them.[34][35] Several mycotoxins reduce milk yield when ingested by dairy cattle.[34]
Contamination of medicinal plants with mycotoxins can contribute to adverse human health problems and therefore represents a special hazard.[36][37] Numerous natural occurrences of mycotoxins in medicinal plants and herbal medicines have been reported[38][39] from various countries including Spain, China, Germany, India, Turkey and from the Middle East.[36] In a 2015 analysis of plant-based dietary supplements, the highest mycotoxin concentrations were found in milk thistle-based supplements, at up to 37 mg/kg.[40]
Some of the health effects found in animals and humans include death, identifiable diseases or health problems, weakened immune systems without specificity to a toxin, and as allergens or irritants. Some mycotoxins are harmful to other micro-organisms such as other fungi or even bacteria; penicillin is one example.[41] It has been suggested that mycotoxins in stored animal feed are the cause of rare phenotypical sex changes in hens that causes them to look and act male.[42][43] Mycotoxins impact on health may be "very hard" and can be categorized in three forms "as mutagenic, carcinogenic, and genotoxic."[44]
Mycotoxicosis is the term used for poisoning associated with exposures to mycotoxins. Mycotoxins have the potential for both acute and chronic health effects via ingestion, skin contact,[45] inhalation, and entering the blood stream and lymphatic system. They inhibit protein synthesis, damage macrophage systems, inhibit particle clearance of the lung, and increase sensitivity to bacterial endotoxin.[25] Testing for mycotoxicosis can be conducted using immunoaffinity columns.[46]
The symptoms of mycotoxicosis depend on the type of mycotoxin; the concentration and length of exposure; as well as age, health, and sex of the exposed individual.[15] The synergistic effects associated with several other factors such as genetics, diet, and interactions with other toxins have been poorly studied. Therefore, it is possible that vitamin deficiency, caloric deprivation, excessive alcohol use, and infectious disease status can all have compounded effects with mycotoxins.[15]
Mycotoxins greatly resist decomposition or being broken down in digestion, so they remain in the food chain in meat and dairy products. Even temperature treatments, such as cooking and freezing, do not destroy some mycotoxins.[47]
In the feed and food industry it has become common practice to add mycotoxin binding agents such as montmorillonite or bentonite clay in order to effectively adsorb the mycotoxins.[48] To reverse the adverse effects of mycotoxins, the following criteria are used to evaluate the functionality of any binding additive:
Since not all mycotoxins can be bound to such agents, the latest approach to mycotoxin control is mycotoxin deactivation. By means of enzymes (esterase, de-epoxidase), yeast (Trichosporon mycotoxinvorans), or bacterial strains (Eubacterium BBSH 797 developed by Biomin), mycotoxins can be reduced during pre-harvesting contamination. Other removal methods include physical separation, washing, milling, nixtamalization, heat-treatment, radiation, extraction with solvents, and the use of chemical or biological agents. Irradiation methods have proven to be effective treatment against mold growth and toxin production.[48]
Many international agencies are trying to achieve universal standardization of regulatory limits for mycotoxins. Currently, over 100 countries have regulations regarding mycotoxins in the feed industry, in which 13 mycotoxins or groups of mycotoxins are of concern.[49] The process of assessing a regulated mycotoxin involves a wide array of in-laboratory testing that includes extracting, clean-up columns[50] and separation techniques.[51] Most official regulations and control methods are based on high-performance liquid techniques (e.g., HPLC) through international bodies.[51] It is implied that any regulations regarding these toxins will be in co-ordinance with any other countries with which a trade agreement exists. Many of the standards for the method performance analysis for mycotoxins is set by the European Committee for Standardization (CEN).[51] However, one must take note that scientific risk assessment is commonly influenced by culture and politics, which, in turn, will affect trade regulations of mycotoxins.[52]
Food-based mycotoxins were studied extensively worldwide throughout the 20th century. In Europe, statutory levels of a range of mycotoxins permitted in food and animal feed are set by a range of European directives and EC regulations. The U.S. Food and Drug Administration has regulated and enforced limits on concentrations of mycotoxins in foods and feed industries since 1985. It is through various compliance programs that the FDA monitors these industries to guarantee that mycotoxins are kept at a practical level. These compliance programs sample food products including peanuts and peanut products, tree nuts, corn and corn products, cottonseed, and milk. There is still a lack of sufficient surveillance data on some mycotoxins that occur in the U.S.[53] 781b155fdc